We plan to continue evaluation of a clinically distinct inherited form of male pseudohermaphroditism in a large group of individuals from a small village in the Dominican Republic. We will also evaluate sporadic and familial cases which appear to have the same clinical condition. By using in vitro and in vivo techniques to study testosterone metabolism we will test the hypothesis that the abnormality of sexual differentiation and development is the result of decreased production of dihydrotestosterone due to a deficiency in steroid delta4 5alpha reductase activity. Investigation of the mode of inheritance of the enzyme defect through extensive pedigree studies, as well as studies of steroid metabolism to identify the carriers will also be carried out. Upon identification of the heterozygotes, genetic counseling will be possible. Evaluation of the response to administered 5alpha dihydrotestosterone in the post-pubertal affected males will be done to elucidate the actions of dihydrotestosterone in puberty, in particular to initiate beard growth. Careful psychosexual evaluation of the affected males will be performed in order to understand their ability to change gender identity at the time of puberty. In addition, we plan to evaluate the role of 5alpha dihydrotestosterone in regulation of control of gonadotropin secretion by comparing response of plasma LH and FSH and testosterone, androstenedione, and 17alpha-OH progesterone to continuous infusion of dihydrotestosterone at two different dose levels. BIBLIOGRAPHIC REFERENCES: Imperato-McGinley, J., and Peterson, R.E.: Male Pseudohermaphroditism: Complexities of Male Sexual Development. Amer. J. Med. 61:251, 1976. Peterson, R.E., and Imperato-McGinley, J.: Male Pseudohermaphroditism Due to Steroid 5alpha-Reductase Deficiency. Amer. J. Med. 62:170, 1977.